Acrolein cyanohydrins are industrially important raw materials.
An important application of these compounds is the synthesis of phosphinothricin (2-amino-4-[hydroxy(methyl)phosphinoyl]butyric acid, vulgo “glufosinate”, or glufosinate salts (EP 0 546 566 A1).
U.S. Pat. Nos. 4,521,348, 4,599,207, 6,359,162 B1, CN 102372739 A, CN 102399240 A, CN 101830926 A describe methods for preparing glufosinates and similar compounds. DE 23 02 523 A1 mentions a similar method in which ethane-1,2-diphosphinic acid diester is obtained from phosphorous acid esters and acetylene, S. R. Piettre, Tetrahedron Letters, 3 (13), 2233-2236 describes similar compounds comprising phosphonyl groups and preparation thereof.
Glufosinates are mainly used as herbicides (EP 0 377 870 A1, U.S. Pat. No. 4,168,963). In addition, EP 0 029 168 A1 mentions the use of similar phosphorus compounds for preparing copolymers in the field of photography.
An essential step in the synthesis of the glufosinates is the addition of a phosphinic acid ester to the double bond of acrolein cyanohydrin (“AcCH” below) or acrolein cyanohydrin acetate (“ACA”). In this reaction in many methods of the prior art, ACA protected by an acetate group is used, obtainable by a method according to EP 0 019 227 A1, e.g. in EP 0 011 245 A1, EP 0 127 877 A2. The reaction using the protected derivative avoids undesired side reactions. On the other hand, it leads to further disadvantages as described in the prior art. WO 2015/173146 A1 discusses the by-products which correlate with the acetylation of the OH function of the cyanohydrin or the omission thereof (WO 2015/173146 A1, page 4, lines 8-24).
In addition, it has already been recognized in DE 30 47 024 A1 that AcCH unprotected on the OH group may also be used in this reaction. Especially when this unprotected AcCH is used as reactant, instead of ACA, the highest possible purity of the same is very important.
AcCH is typically obtained by reaction of acrolein and hydrocyanic acid (U.S. Pat. No. 3,850,976.) The problem which occurs here is that a certain residue of the hydrocyanic acid reactant is always found in the AcCH obtained. This is even more so the case when an excess of hydrocyanic acid is used, based on acrolein, which is customary due to the desired as complete as possible conversion of the acrolein.
This residual content of hydrocyanic acid causes several problems however: for instance, it results in undesired side reactions in the subsequent synthetic sequence. This is especially problematic in the synthesis of glufosinates, and has already been noted in the prior art (WO 2015/173146 A1: page 2, line 15). In addition, hydrocyanic acid is toxic and can react explosively, particularly since a peroxide is present in the subsequent step which leads to release of oxygen. It is therefore also undesirable for the point of view of operational safety that free hydrocyanic acid is present in the AcCH.
The prior art describes several methods for removing the hydrocyanic acid—however these are quite cumbersome or cause further problems. The reason for this is that the treatment of AcCH is problematic and AcCH cannot be simply subjected to customary purification methods due to its instability.
This previous provision of hydrocyanic acid-free AcCH entails the following steps according to conventional methods:
a) acetylation of the crude AcCH contaminated with hydrocyanic acid to ACA and purification (described for example in EP 0 019 750 A1);
b) deacetylation of the ACA via ion exchange (as described in Example 1 of WO 2015/173146 A1, page 17, lines 12-22).
This means that up to now the provision of hydrocyanic acid-free AcCH cannot circumvent the acetylation. The acetic acid released both in the acetylation and in the deacetylation itself leads to further impurities in the AcCH obtained after the deacetylation. These impurities may again lead to side reactions in the subsequent steps of the synthesis.
A further disadvantage of the hydrocyanic acid removal described above is that it is very expensive due to the costly use of an ion exchanger.
There exists a need, particularly in the synthesis of glufosinates, to omit the acetylation of the (intermediate) product AcCH, and still to be able to use this as free of hydrocyanic acid as possible.
Accordingly, the object of the present invention was to provide an improved synthetic route for preparing acrolein cyanohydrin and similar compounds compared to the prior art. This synthesis should lead especially to products having lower impurities, in particular a lowest possible fraction of hydrocyanic acid, and at the same time to avoid the disadvantages of the methods of the prior art.
The invention achieves this object and, surprisingly, shows an efficient alternative way to remove these by-products and to more easily obtain pure AcCH.